B67 tumors of the exocrine and endocrine pancreats Flashcards
Types of exocrine pancreas tumors
Cystic neoplasms, 10% of exocrine neoplasms
- Serous Cystadenoma
- Mucinous Cystadenoma -> Mucinsous cystic tumor with moderate dysplasia -> Mucinous Cystadenocarcinoma
Other types
- Intraductal Papillary Mucinous Adenoma -> IPMA with dysplasia -> Itraductal papillary mucinous carcinoma
- Solid pseudopapillary tumor -> solid pseudopapillary carcinoma
- Ductal adenocarcinomas
Tumors of the endocrine pancreas and their frequency
PanNETs, pancreatic neuroendocrine tumors. They are rare compared to tumors of the exocrine pancreas. 2% of all pancreas tumors.
Insulinomas are the vast majority.
Glucagonomas are rare
VIPomas are rare
Somatostatinomas are rare
Serous cystadeonmas prevalence, prognosis
25% of all cystic pancreas neoplasms.
Virtually always benign
2:1 female preference
Present late, in the 60’s or later
Curative by surgical resection
Most of them have VHL mutations.
Seous cystadenocarcinoma morphology, histology
Morphology:
- can be very large, obstructing most of the normal pancreas,
- Forms extremely numerous small cysts, a few mm in diameter. and lots of fibrous septa in between.
Histology:
- Tumor is composed entirely of cysts and mostly acellular, fibrous stroma
- Cysts are lined by cuboidal epithelium that look well differentiated with no atypia.
Mucinous cystic neoplasms
95% are in women
Slow growing tumors that arise in the body and tail.
Cystic spaces are filled with thick mucin, and lined by a columnar epithelium (instead of the cuboidal one in serous cystadenoma)
The stroma surrounding the cysts is densely cellular and is said to resemble ovarian tissue, though it has no relation.
These are classified into 3 categories, low, moderate, or severe, based on the degree of dysplasia in the cells and in the ceullular organization of the epithelium. The moderate/severely dysplastic mucinous cystic neoplasms are borderline tumors, displaying atypia, but no invasion. 1/3rd are associated with invasive adenocarcinoma
If invasion has not occured, distal pancreatectomy is curative.
Intraductal papillary mucinous neoplasms
IPMNs, in contrast to mucinous cystic neoplasms, occur in men, and in the head of the pancreas.
Arise in the main pancreatic duct or its major branches
Does not have a cellular stroma,
Forms papillary extensions of mucinous epithelium into the lumen of the pancreatic duct. Distending it and obstructing it. It eventually spreads from the main duct throughout all of the ducts.
The epithelium that is formed in IPMNs can have low, moderate, or severe dysplasia, just as the mucinous cystic neoplasm.
Some of IPMNs are associated with invasive adenocarcinoma
2/3rds have mutations to the GNAS gene, the alpha subunit of Gs protein.
Pancreatic carcinoma
morphology, histology
Infiltrating ductal adenocarcinoma = “pancreatic carcinoma”
Morphology:
- 60% form in the head, 15% in the body, 5% in the tail
- 20% form diffusely involving the whole pancreas.
- Hard
- Gray
- Stellate/irregular masses
- elicits a strong desmoplastic reaction - making it very hard.
- Are extremely invasive, have almost alwasy invaded peri-pancreatic tissues even at ‘early’ stages
- locally invading to the spleen, adrenals, vertebrae, transverse colon, and stomach
- metastases to the liver, lung and other bones are also very common.
- can also invade nerves and cause pain as a presenting symptom.
Histology:
- Cellular tumor little/no stroma
- A poorly differentiated adenocarcinoma
- abortive tubular structures
- infiltrative cell clusters.
- The area around the tumor exhibits the dense desmoplasstic reaction.
- Perineural invasion is common
- lymphatic invasion also common.
Rare variants include
- adenosquamous carcinoma; with focal squamous differentiation areas
- undifferentiated carcinomas; with osteoclast-like giant cells and monocytes mixed with the neoplasm.
Pancreatic carcinoma, presentation, prognosis, treatment
Presentation:
- They are silent until they impinge some other structure
- Pain is often the first symptom, due to perineural infiltration or compression of a nerve in the retroperitoneum. This carries a very bad prognosis.
- Obstructive jaundice if it is in the pancreatic head, but this also usually occurs too late for useful intervention.
- General symptoms are often the first sign, weight loss, malaise, weakness, night sweat, and indicate advanced stage as well.
- Migratory thrombophlebitis, Trousseaus sign. Seen in about 10% of patients. due to platelet aggregating factors, procoagulants from the tumor or their necrotic products.
Prognosis:
- only 20% are surgically resectable at time of diagnosis
- treatments is chemotherapy
- There is not a significantly useful biomarker or screening tool for early pancreatic cancer
- Progression is rapid and 5 year survival is less than 5%. it is virtually always fatal.
- Pancreatic carcinoma is much less common than most other cancers but has an extremely high mortality rate.
Mutations associated with pancreatic carcinoma
progressive accumulation of characteristic mutations of
oncogenes (e.g., KRAS, activating mutation) and tumor suppressor genes (e.g.,
CDKN2A/p16, TP53, and SMAD4, inactivating).
What are the types of endocrine pancreas tumors?
- Pancreatic islet cell tumors, aka PanNETs, Pancreatic Neuroendocrine tumors
- 2% of all pancreatic neoplasms, occur mostly in adults
- May be single or multifocal
- Metastsize to the liver
- Can secrete pancreatic enzymes or be non-secretory, non-secretory ones present with mass effects or obstruciton of pancreatic head, and general symptoms of a large neoplasm, bad prognosis.
- All have malignant potential, and 65-80% are overtly malignant from the start. except pancreatic insulinomas.
- The proliferative/mitotic counts using Ki-67 is the best predictor of outcome.
- Are often part of MEN1 syndrome.
- Loss of PTEN or TSC2 tumor suppressor genes, disinhibition of the mTOR oncogenic pathway.
- 50% have ATRX or DAXX mutations, but rarely both. indicating that they are a critical and overlapping function.
- Insulinomas have high 90% 5yrS
- Gastrinomas 50-70
- vipoma glucagonoma 40-60%
- somatostatinoma 20-40%
- non-secretory 30-50%
Beta cell tumors, insulinomas, general features, morphology, histology
Are the most common type of inslet cell tumor
Secrete functional insulin and can produce clinical hypoglycemia.
Whipples triad, fasting hypoglycemia and clinical symptoms, rapidly curing by dextrose administration. indicates insulinoma.
Insulinomas are not malignant and are usually cured by surgical resection., probably because their symptoms cause such an early presentation, they are usually identified at less than 2cm in diameter
Usually solitary,but can also be multifocal or ectopic from the pancreas: wall of the stomach, duodenum, followed by jejunum, Meckels, and ileum
Malignant insulinomas do occur, at less than 10% of all insulinomas. Malignancy is based on local invasion or metastases.
Histologically they look like huge islets, with regular cords of cells and normal vasculature organization, and normal granulation of islet cells. Even malignant ones have minimal anaplasia, and may be encapsulated.
Extracellular amyloid deposition is seen in many insulinomas
Gastrinomas
Arise in the:
duodenum
pancreas
peri-pancreatic soft tissue.
The high gastrin excretion causes Zollinger-Ellison syndrome:
- excessive gastric acid secretion
- severe peptic ulceration, multiple ulcers
- these ulcers are unresponsive to normal therapy,
- occur in unusual locations, ie, the jejunum –> this is very strongly indicative of gastrinoma.
- diarrhea due to excessive gastric motility
These are very often malignant, over half have metastasized at presentation/diagnosis.
25% are part of MEN-1 syndrome. MEN-1 associated gastrinomas are often multifocal and sporadic ones are usually single.
Like insulinomas, they histologically look like well differentiated pancreatic islet cells, rarely any anaplasia. Despite this they are usually malignant, 60-80%.
Glucagonomas
Rare alpha cell tumor
Secondary type 2 diabetes mellitus
the hallmark symptoms is: Necrolytic migratory erythema, seen in 70%
Erythematous, blisters and red swelling across areas of friction, abdomen, perineum, groin, axillae, mouth.
Diagnosis: high blood serum glucagon levels, with normo/hyperglycemia.
Octreotide inhibition is used for treatment, . Octreotide is a somatostatin analog, and suppresses glucagon release to manage symptoms.
Treatment is surgical resection
VIPoma
rare. VIP secretion
pancreatic cholera
watery diarrhea, hypokalemia, achlorhydria.
Hypokalemia symptoms
- Symptoms occur if plasma K+ is < 3.0 mmol/L
- Weak and tired legs
- Fatigue
- Myalgias
- Hypoventilation due to respiratory muscle weakness
- Paralysis
- Nocturia, polyuria, polydipsia
Somatostatinomas
Achlorhydria - due to gastin secretion
Cholelithiasis - due to cholecystokinin inhibition
Steatorrhea - also due to cholecystokinin
Lipid malabsorption syndrome, due to no bile secretion
